Aphthous ulcers are the most common oral mucosal lesions in the general population. Several precipitating factors for aphthous ulcers are suggested to operate on subjects with genetic predisposition. Sometimes aphthous ulcers can be the sign of systemic diseases. Therefore, it is essential to establish a correct diagnosis to determine suitable therapy. There are several diseases potentially responsible for oral ulcers. Sometimes appearance of periodic oral ulcers coincides with periodic fever and other symptoms leading to the diagnosis of a rare childhood disease: PFAPA (periodic fever, aphthous stomatitis, pharyngitis and adenopathy) syndrome. PFAPA or Marshall's syndrome is characterized by abrupt onset of periodic episodes of high fever accompanied by aphthous stomatitis, pharyngitis and cervical adenitis, often associated with headache and / or abdominal or joint pain. Owing to the periodic onset of oral symptoms, often an oral physician or pediatric dentist may be the first healthcare worker to evaluate a child with clinical signs compatible with PFAPA syndrome. Children diagnosed with this condition require systematic oral follow-up to monitor for signs of ulceration.